We are studying the interaction of several ligands with short, DNA triplexes to examine the effect of sequence, cations and base modifications. Several types of triplexes have been examined, such as thos e with third strands composed of pyrimidines or purines or a mixture of guanine and thymine. While most of the intercalators we studied can bind to these triplexes, they tend to prefer binding to the duplexes. MidasPlus is of great utility in visualizing the types of interactions that can occur with triplexes.